1. Early Postnatal Death and Motor Disorders in Mice Congenitally Deficient in Calnexin Expression
- Author
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Joanne E. Martin, Angela Denzel, Maurizio Molinari, Michael John Owen, Shanti Velmurgan, Susan J. Brown, César Trigueros, and Gordon Stamp
- Subjects
Heterozygote ,Protein Folding ,Glycan ,Time Factors ,Calnexin ,Cell Survival ,Endoplasmic Reticulum ,Transfection ,Nerve Fibers, Myelinated ,Mice ,Mammalian Genetic Models with Minimal or Complex Phenotypes ,Animals ,Molecular Biology ,Alleles ,Myelin Sheath ,Gene knockout ,Mice, Knockout ,Motor Neurons ,Recombination, Genetic ,chemistry.chemical_classification ,Models, Genetic ,biology ,Stem Cells ,Endoplasmic reticulum ,Cell Biology ,Embryo, Mammalian ,Molecular biology ,Cell biology ,Mice, Inbred C57BL ,Microscopy, Electron ,Phenotype ,Animals, Newborn ,chemistry ,Membrane protein ,Chaperone (protein) ,biology.protein ,Protein folding ,Glycoprotein ,Molecular Chaperones - Abstract
Calnexin is a ubiquitously expressed type I membrane protein which is exclusively localized in the endoplasmic reticulum (ER). In mammalian cells, calnexin functions as a chaperone molecule and plays a key role in glycoprotein folding and quality control within the ER by interacting with folding intermediates via their monoglucosylated glycans. In order to gain more insight into the physiological roles of calnexin, we have generated calnexin gene-deficient mice. Despite its profound involvement in protein folding, calnexin is not essential for mammalian-cell viability in vivo: calnexin gene knockout mice were carried to full term, although 50% died within 48 h and the majority of the remaining mice had to be sacrificed within 4 weeks, with only a very few mice surviving to 3 months. Calnexin gene-deficient mice were smaller than their littermates and showed very obvious motor disorders, associated with a dramatic loss of large myelinated nerve fibers. Thus, the critical contribution of calnexin to mammalian physiology is tissue specific.
- Published
- 2002